Medical imaging

If the RatCAP fits...

Mar 14th 2011, 18:15 by The Economist online

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ONE of the biggest advances in medical imaging made in recent decades is positron emission tomography (PET). This technique looks beyond mere anatomy and produces a three-dimensional picture of the body’s biochemical processes. It has become particularly popular in neuroscience. Using PET scanners to study what is going on in the brains of animals other than humans, though, has proved difficult. Whereas people can be told to relax as they are passed through a large doughnut-shaped scanner, animals have to be immobilised—and this is typically done by administering a general anaesthetic. The problem is that anaesthesia disrupts brain function, so researchers may not see a true picture. Now a PET scanner has been developed that is small and light enough to be worn on the head of a laboratory rat, allowing its brain to be studied as it moves around.

The device, created by Paul Vaska of the Brookhaven National Laboratory in Upton, New York, and his colleagues, and described in Nature Methods, is called the RatCAP (Rat Conscious Animal PET). Although some smallish PET scanners have been produced in the past, nothing as diminutive as the RatCAP has been made before. The doughnut has an outer diameter of 80mm and an inner one of 38mm. That is possible because the device uses miniaturised electronics, including tiny gamma-ray detectors, developed especially for it. Though it weighs 250 grams, which would be too heavy for a rat to support unaided, part of that weight is carried by a mechanism made of springs and bearings which is suspended from the roof of the experimental chamber and attached to the RatCAP by cables. Within the confines of this chamber, then, the rat can move freely around.

As with bigger PET scanners, the RatCAP works in conjunction with radioactive biochemicals called radiotracers that are injected into the body. Each molecule of a PET radiotracer includes an atom of a radioactive isotope such as fluorine-18 or oxygen-15 that decays to release a positron, the antimatter equivalent of an electron. When the isotope in the tracer decays, the emitted positron quickly encounters an electron and the two annihilate each other in a burst of gamma rays. These are picked up by the gamma-ray detectors, allowing the location and concentration of the tracer to be identified and displayed as a three-dimensional image—for different types of radiotracer accumulate in different parts of the body. To test the system, Dr Vaska and his colleagues used a radiotracer that binds to receptors for dopamine, a brain chemical involved in movement, reward and memory. 

In the case of Dr Vaska’s dopamine analogue, a stronger signal is usually interpreted as meaning that less natural dopamine is present in that part of the brain (because the tracer binds to unoccupied receptors, of which fewer are available when a lot of dopamine is around). What the researchers found, though, surprised them. They expected active animals to have high dopamine levels. They discovered the inverse: the more active an animal is, the lower its level of dopamine, as indicated by the tracer signals. 

That was a counterintuitive result, according to Dr Vaska’s colleague Daniela Schulz, who led the dopamine study, and more work will be needed to explain it. Nevertheless, the RatCAP project has demonstrated that is possible to use PET to measure neural function and behaviour in a conscious, freely moving animal. And that could turn up many new insights into how the brain works.

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